The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It ha...The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).展开更多
During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World J Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas i...During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World J Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas in humans.Agenesis of the dorsal pancreas,a rare congenital pancreatic malformation,is associated with some other medical conditions such as hyperglycemia,abdominal pain,pancreatitis and a few other diseases.In approximately 50% of reported patients with this congenital malformation,hyperglycemia was demonstrated.Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose,oral glucose tolerance test,glycated hemoglobin and medical treatment would be a future goal.Since autosomal dominant transmission has been suggested in single families,more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease.With this letter to the editor,we aim to increase available information for the better understanding of this rare disease.展开更多
Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genom...Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genomic pathway of testosterone and estradiol in the amygdala in relation to anxiety and depressive-like behavior. Sham-operated and gonadectomized male rats （GDX） supplemented with testosterone propionate, estradiol, or olive oil were used. Five minutes after administration, anxiety and depression-like behavior were tested. Estradiol increased anxiolytic behavior in the open-field test compared to the GDX group, but administration of testosterone had no significant effect. Besides, c-Fos expression in the medial nucleus of the amygdala significantly increased after testosterone treatment compared to the GDX group, while no significant difference was observed in the central and the basolateral nuclei of the amygdala in the testosterone-treated group compared to the GDX group. In conclusion, estradiol had an anxiolytic effect via a rapid pathway, but no rapid effect of testosterone on anxiety was found. Further studies elucidating whether the rapid effect is mediated by a non-genomic pathway are needed.展开更多
Cardiac resynchronization therapy （CRT） is associated with a favorable outcome only in patients with left bundle branch block （LBBB） pattern and in patients with a QRS duration 〉 150 ms, in patients with non-LBBB...Cardiac resynchronization therapy （CRT） is associated with a favorable outcome only in patients with left bundle branch block （LBBB） pattern and in patients with a QRS duration 〉 150 ms, in patients with non-LBBB pattern with a QRS duration of 120-150 ms usually is not beneficial. After adjusting for QRS duration, QRS morphology was no longer a determinant of the clinical response to CRT. In contrast to the mainstream view, we hypothesized that the unfavorable CRT outcome in patients with non-LBBB and a QRS duration of 120-150 ms is not due to the QRS morphology itself, but to less dyssynchrony and unfavorable patient characteristics in this subgroup, such as more ischemic etiology and greater prevalence of male patients compared with patients with LBBB pattern. Further, the current CRT technique is devised to eliminate the dyssynchrony present in patients with LBBB pattern and inappropriate to eliminate the dyssynchrony in patients with non-LBBB pattern. We also hypothesized that electrocardiography may also provide information about the presence of interventricular and left intraventricular dyssynchrony and the approximate location of the latest activated left ventricular （LV） region. To this end, we devised new ECG criteria to estimate interventricular and LV intraventricular dyssynchrony and the approximate location of the latest activated LV region. Our preliminary data demonstrated that the latest activated LV region in patients with nonspecific intraventricular conduction disturbance （NICD） pattern might be at a remote site from that present in patients with LBBB pattern, which might necessitate the invention of a novel CRT technique for patients with NICD pattern. The application of the new interventricular and LV intraventricular dyssynchrony ECG criteria and a potential novel CRT technique might decrease the currently high nonresponder rate in patients with NICD pattern.展开更多
Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the ne...Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the neuroprotective effect of hydroxysafflor yellow A(HSYA)against chronic mild stress(CMS)-induced memory impairments in mice and the underlying mechanism.The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice.HSYA increased the expression of brain-derived neurotrophic factor(BDNF)and activated downstream tropomyosin-related kinase B(TrkB)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling.HSYA decreased the expression of regulator of calcineurin 1-1L(RCAN1-1L)that could promote the activity of glycogen synthase kinase-3β(GSK-3β).HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3βand cyclin-dependent kinase-5(Cdk5).Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation,tau phosphorylation and memory impairments.HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.展开更多
Objective: To explore the importance of CBL in pathophysiology teaching. Methods: 218 undergraduate clinical medicine students in 2015 grade were divided into CBL group and control group, and each group had 109 studen...Objective: To explore the importance of CBL in pathophysiology teaching. Methods: 218 undergraduate clinical medicine students in 2015 grade were divided into CBL group and control group, and each group had 109 students. The CBL group was taught by CBL, while the control group was taught by routine teaching mode. The teaching effects was evaluated by questionnaire survey and stage test. Results: The CBL group was superior to the control group in learning interest, logical thinking, knowledge system construction, comprehensive use of knowledge to solve problems. Conclusion: CBL teaching enhanced students’ understanding of knowledge significantly, and also enhanced their clinical thinking and problem analysis ability.展开更多
Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with h...Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with hydrogen(H2) breath tests and correlated to carbohydrate malabsorption. During performing these H2-breath tests the patient presented with an acute, localized, non-migratory pain in the left lower abdominal quadrant. Primary epiploic appendagitis is a rare cause of abdominal acute or subacute complaints and diagnosis of primary epiploic appendagitis(PEA) is made when computed tomography reveals a characteristic lesion. We report on a patient with cooccurrence of lactose and fructose malabsorption, which was treated successfully with a diet free of culprit carbohydrates, with PEA recovering without medication or surgical treatment within few days. Since the abdominal unspecific symptoms had been present for months, they appeared not to be correlated to the acute localized abdominal pain, therefore we speculate on a random co-occurrence of combined carbohydrate malabsorption and PEA.展开更多
Background: Intravenous application of iron preparations which is a routine treatment of anemia in hemodialysis patients with end-stage renal disease can lead to iron overload in the body. Redox-active iron can cataly...Background: Intravenous application of iron preparations which is a routine treatment of anemia in hemodialysis patients with end-stage renal disease can lead to iron overload in the body. Redox-active iron can catalyze the formation of hydroxyl radicals and initiation of lipid peroxidation, increase oxidative stress and speed up the development of complications in these patients. Objective: In this study, we determined the markers of lipid peroxidation, protein oxidation and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione S-transferase) in serum of patients with end-stage renal disease on hemodialysis, who had received repeated treatment of iron supplementation. Patients and Methods: The study included 29 patients undergoing regular hemodialysis treatment. These patients were divided into three groups according to the serum ferritin levels: group I (serum ferritin between 100 and 300 mg/L);group II (serum ferritin between 301 and 600 mg/L), and group III (serum ferritin above 601 mg/L). Results: The serum of patients with the highest concentration of serum ferritin and iron contained significantly higher level of lipid peroxidation products, total hydroperoxides and malondialdehyde and advanced oxidation protein products and the lowest concentration of sulfhydryl groups, reduced glutathione and total antioxidant capacity. Conclusion: Based on the obtained results, it can be concluded that iron supplementation in hemodialysis patients and consequently body iron overload of exacerbated oxidative stress have already been present in these patients.展开更多
The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointesti...The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointestinal tract, where it is ubiquitously expressed. In the colon, the CaSR is involved in controlling multiple mechanisms, including fluid transport, inflammation, cell proliferation and differentiation. Although the expression pattern and functions of the CaSR in the colonic microenvironment are far from being completely understood, evidence has been accumulating that the Ca SR might play a protective role against both colonic inflammation and colorectal cancer. For example, CaSR agonists such as dipeptides have been suggested to reduce colonic inflammation, while dietary calcium was shown to reduce the risk of colorectal cancer. CaSR expression is lost in colonic malignancies, indicating that the CaSR is a biomarker for colonic cancer progression. This dual anti-inflammatory and anti-tumourigenic role of the CaSR makes it especially interesting in colitisassociated colorectal cancer. In this review, we describe the clinical and experimental evidence for the role of the CaSR in colonic inflammation and colorectal cancer, the intracellular signalling pathways which are putatively involved in these actions, and the possibilities to exploit these actions of the CaSR for future therapies of colonic inflammation and cancer.展开更多
AIM: To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.
Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction ...Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.展开更多
Synthetic biology is the design and construction of new biological parts,devices,and systems,and the re-design of existing,natural biological systems for useful purposes.This new interdisciplinary effort has gained in...Synthetic biology is the design and construction of new biological parts,devices,and systems,and the re-design of existing,natural biological systems for useful purposes.This new interdisciplinary effort has gained interest from the industry sector,and synthetic biology has been used to produce fragrances,such as vanillin in yeast,in cells that do not normally exist in nature.展开更多
Despite progresses achieved in the therapy of tumors, the prognosis of patients is still limited by reccurence of residual tumor cells. Cancer cell dormancy plays a pivotal role in cancer relapse and drug resistance. ...Despite progresses achieved in the therapy of tumors, the prognosis of patients is still limited by reccurence of residual tumor cells. Cancer cell dormancy plays a pivotal role in cancer relapse and drug resistance. In recent years, tumor cells undergoing EMT(epithelial-mesenchymal transition), CSCs(cancer stem cells) and CTCs(circulating tumor cells) are proved to share some common characteristics and show a cell cycle arrest phenotype. Thus, understanding the dormant stage of tumor cells could facilitate us in discovering ways to accelerate the development of tumor therapy and prevent its reccurence. In this review, we summarize the specific process of tumor cell dormancy induced by pharmacotherapy, and consider that dormancy is an initiative response rather than a passive defense to cytotoxicity. Besides, we probe into the mechanisms of tumor cell dormancy-mediated drug resistance, anticipating paving a way to target dormant tumor cells and result in better clinical outcomes.展开更多
Complement activation-related pseudoallergy (CARPA) is a frequent side effect of intravenous therapies with nanoparticle-containing drugs and biologicals that are recognized by the immune system as foreign. It is an a...Complement activation-related pseudoallergy (CARPA) is a frequent side effect of intravenous therapies with nanoparticle-containing drugs and biologicals that are recognized by the immune system as foreign. It is an acute infusion reaction dominated by cutaneous and hemodynamic changes, most significantly a cardiopulmonary distress involving major pulmonary hypertension, systemic hypotension and arrhythmias. Because CARPA is unpredictable by conventional allergy tests and it may be life threatening, it can represent a major barrier to the safe therapeutic application of many modern medicines, including liposomal drugs and monoclonal antibodies. This review summarizes and updates the facts and opens questions regarding this phenomenon, with particular focus on its porcine model.展开更多
Introduction: Pelvic floor muscle function of 30 overweight postmenopausal women prior to and after colporrhahpy was monitored in this study. Material and Methods: Patients diagnosed with cystokele or combined cystore...Introduction: Pelvic floor muscle function of 30 overweight postmenopausal women prior to and after colporrhahpy was monitored in this study. Material and Methods: Patients diagnosed with cystokele or combined cystorectokele was involved. 1 mg oral estriol and local estriol cream were administered for 30 days preoperatively. Pelvic floor muscle function was monitored by surface electromyography 1 month before (1st) 1 day prior to surgery (2nd), and six weeks after the surgery (3rd measurement). Body composition parameters (intra- and extracellular water and body fat) were also measured. Results: The ability to relax significantly improved (p = 0.03) in the preoperative period (between 1st and 2nd occasions). Six weeks after surgery a non-significant (p = 0.054) decrease in average muscle activity was detected when compared with values obtained before the surgery. Muscle-activity declined significantly from the first to the last measurements (p = 0.005). Conclusion: Our results confirm that postmenopausal obese women who undergo anterior or posterior colporrhaphy need a follow-up concerning pelvic floor muscle function and suggest that physiotherapy started the earliest possible may aid in preserving postoperative functionality on the long run.展开更多
The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine...The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine were injected in the nose, and mechanical nylon fiber and/or air puff stimulation was applied to the nose and nasopharynx. Reflex responses of cough, sneeze, aspiration reflex and expiration reflex were induced mechanically. Swallow was initiated by the injection of water into oropharynx. Subthreshold mechanical stimulation of nasopharyngeal and nasal mucosa, as well as water stimulation in the oropharynx and larynx, with no motor response, had no effect on rhythmic coughing. Cough responsiveness and excitability increased with capsaicin and air puff stimuli delivered to the nose. Vice versa, the number of cough responses was reduced and cough latency increased when aspiration reflexes (>1) occurred before the cough stimulus or within inter-cough intervals (passive E2 cough phase). The occurrence of swallows increased the cough latency as well. Cough inspiratory and/or expiratory motor drive was enhanced by the occurrence of expiration reflexes, swallows, and sneezes and also by aspiration reflex within the inspiratory phase of cough and by nasal air puff stimuli. Complex central interactions, ordering and sequencing of motor acts from the airways may result in the disruption of cough rhythmic sequence but also in the enhancement of cough. Our data confirm that number of peripheral stimuli and respiratory motor responses significantly alters cough performance. We propose developing and testing stimulation paradigms that modify coughing and could be employed in correcting of inappropriate or excessive coughing.展开更多
Background: Multiple organ dysfunction syndrome(MODS) is the sequential failure of several organ systems after a trigger event, like cardiogenic shock or decompensated heart failure. Mortality is high, up to 70% . Aut...Background: Multiple organ dysfunction syndrome(MODS) is the sequential failure of several organ systems after a trigger event, like cardiogenic shock or decompensated heart failure. Mortality is high, up to 70% . Autonomic dysfunction(AD)may substantially contribute to the development of MODS. In cardiology, it has recently been shown that nonlinear parameters could predict mortality.Our study aimed at 1. characterising the complex characteristics of AD of critically ill MODS patients by the nonlinear parameters of autonomic information flow(AIF), 2. comparing AIF with autonomic function of healthy controls, and 3. characterising the accuracy of this parameter in predicting mortality in MODS. Methods: We enrolled 43 score-defined MODS patients who were consecutively admitted to a twelve-bed medical intensive care unit in a university centre into this prospective outcome study. Additionally, we assigned 50 healthy controls to the study. AIF was assessed as a complexity function of AD using 24-h ECG. Measures of AIF were introduced according to the standard HRV concept. The patients were followed up for 28-day mortality. Results: MODS causes a disorganisation of short term AIF in favour of an enhanced(rigid) long term AIF. Concerning prognosis increased short term AIF was associated with survival. Short term AIF discriminated between MODS survivors and nonsurvivors at the level of APACHE II score. Conclusions: This is the first study providing evidence that complex AD of MODS patients is specifically assessed by AIF time scales and that AIF has significant prognostic impact.展开更多
Background：The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding.Our purpose was to investigate the effects of 5-fluorouracil （5-FU） on ten...Background：The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding.Our purpose was to investigate the effects of 5-fluorouracil （5-FU） on tendon adhesions in partially divided profundus flexor tendons （flexor digitorum profundus [FDPs]） following surgical repair and in partially divided FDPs without surgical repair,and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions.Methods：We used 32 adult male European rabbits （Oryctolagus cunniculus） weighing from 2.5 to 3.5 kg.The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits;thus,a total of 64 tendons were examined in this study.Results：Based on the results achieved in our experimental study,the load （N） significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU.Conclusions：The load （N） significantly increased in subgroup 1 a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU.Therefore,these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath,which in this case required greater traction force.展开更多
Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsych...Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome.Pathophysiological changes in astroglia can be primary or secondary and can result in gain or loss of functions.Astroglia respond to external,non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure,molecular expression,and function.In addition,internally driven,cell autonomous changes of astroglial innate properties can lead to CNS pathologies.Astroglial pathophysiology is complex,with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder,disorder-stage,comorbidities,age,and sex.Here,we classify astroglial pathophysiology into(i)reactive astrogliosis,(ii)astroglial atrophy with loss of function,(iii)astroglial degeneration and death,and(iv)astrocytopathies characterised by aberrant forms that drive disease.We review astroglial pathophysiology across the spectrum of human CNS diseases and disorders,including neurotrauma,stroke,neuroinfection,autoimmune attack and epilepsy,as well as neurodevelopmental,neurodegenerative,metabolic and neuropsychiatric disorders.Characterising cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies.展开更多
文摘The concept of the brain cognitive reserve is derived from the well-acknowledged notion that the degree of brain damage does not always match the severity of clinical symptoms and neurological/cognitive outcomes.It has been suggested that the size of the brain(brain reserve) and the extent of neural connections acquired through life(neural reserve) set a threshold beyond which noticeable impairments occur.In contrast,cognitive reserve refers to the brain's ability to adapt and reo rganize stru cturally and functionally to resist damage and maintain function,including neural reserve and brain maintenance,resilience,and compensation(Verkhratsky and Zorec,2024).
文摘During the last 100 years in medical literature,there are only 54 reports,including the report of Pasaoglu et al(World J Gastroenterol 2008;14:2915-2916),with clinical descriptions of agenesis of the dorsal pancreas in humans.Agenesis of the dorsal pancreas,a rare congenital pancreatic malformation,is associated with some other medical conditions such as hyperglycemia,abdominal pain,pancreatitis and a few other diseases.In approximately 50% of reported patients with this congenital malformation,hyperglycemia was demonstrated.Evaluation of hyperglycemia and diabetes mellitus in all patients with agenesis of the dorsal pancreas including description of fasting blood glucose,oral glucose tolerance test,glycated hemoglobin and medical treatment would be a future goal.Since autosomal dominant transmission has been suggested in single families,more family studies including imaging technologies with demonstration of the pancreatic duct system are needed for evaluation of this disease.With this letter to the editor,we aim to increase available information for the better understanding of this rare disease.
基金supported by a VEGA grant (1/0406/13)the Ministry of Education of Slovak Republicthe APVV-0753-10 and the UK/384/2013
文摘Besides their known slow genomic effects, testosterone and estradiol have rapid effects in the brain. However, their impact on mood-related behavior is not clear. The aim of this study was to investigate the non-genomic pathway of testosterone and estradiol in the amygdala in relation to anxiety and depressive-like behavior. Sham-operated and gonadectomized male rats （GDX） supplemented with testosterone propionate, estradiol, or olive oil were used. Five minutes after administration, anxiety and depression-like behavior were tested. Estradiol increased anxiolytic behavior in the open-field test compared to the GDX group, but administration of testosterone had no significant effect. Besides, c-Fos expression in the medial nucleus of the amygdala significantly increased after testosterone treatment compared to the GDX group, while no significant difference was observed in the central and the basolateral nuclei of the amygdala in the testosterone-treated group compared to the GDX group. In conclusion, estradiol had an anxiolytic effect via a rapid pathway, but no rapid effect of testosterone on anxiety was found. Further studies elucidating whether the rapid effect is mediated by a non-genomic pathway are needed.
文摘Cardiac resynchronization therapy （CRT） is associated with a favorable outcome only in patients with left bundle branch block （LBBB） pattern and in patients with a QRS duration 〉 150 ms, in patients with non-LBBB pattern with a QRS duration of 120-150 ms usually is not beneficial. After adjusting for QRS duration, QRS morphology was no longer a determinant of the clinical response to CRT. In contrast to the mainstream view, we hypothesized that the unfavorable CRT outcome in patients with non-LBBB and a QRS duration of 120-150 ms is not due to the QRS morphology itself, but to less dyssynchrony and unfavorable patient characteristics in this subgroup, such as more ischemic etiology and greater prevalence of male patients compared with patients with LBBB pattern. Further, the current CRT technique is devised to eliminate the dyssynchrony present in patients with LBBB pattern and inappropriate to eliminate the dyssynchrony in patients with non-LBBB pattern. We also hypothesized that electrocardiography may also provide information about the presence of interventricular and left intraventricular dyssynchrony and the approximate location of the latest activated left ventricular （LV） region. To this end, we devised new ECG criteria to estimate interventricular and LV intraventricular dyssynchrony and the approximate location of the latest activated LV region. Our preliminary data demonstrated that the latest activated LV region in patients with nonspecific intraventricular conduction disturbance （NICD） pattern might be at a remote site from that present in patients with LBBB pattern, which might necessitate the invention of a novel CRT technique for patients with NICD pattern. The application of the new interventricular and LV intraventricular dyssynchrony ECG criteria and a potential novel CRT technique might decrease the currently high nonresponder rate in patients with NICD pattern.
基金the Fundamental Research Funds for the Central Universities(No.lzujbky-2016-70)the Natural Science Foundation of Gansu Province(No.1506RJZA235).
文摘Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the neuroprotective effect of hydroxysafflor yellow A(HSYA)against chronic mild stress(CMS)-induced memory impairments in mice and the underlying mechanism.The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice.HSYA increased the expression of brain-derived neurotrophic factor(BDNF)and activated downstream tropomyosin-related kinase B(TrkB)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling.HSYA decreased the expression of regulator of calcineurin 1-1L(RCAN1-1L)that could promote the activity of glycogen synthase kinase-3β(GSK-3β).HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3βand cyclin-dependent kinase-5(Cdk5).Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation,tau phosphorylation and memory impairments.HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.
文摘Objective: To explore the importance of CBL in pathophysiology teaching. Methods: 218 undergraduate clinical medicine students in 2015 grade were divided into CBL group and control group, and each group had 109 students. The CBL group was taught by CBL, while the control group was taught by routine teaching mode. The teaching effects was evaluated by questionnaire survey and stage test. Results: The CBL group was superior to the control group in learning interest, logical thinking, knowledge system construction, comprehensive use of knowledge to solve problems. Conclusion: CBL teaching enhanced students’ understanding of knowledge significantly, and also enhanced their clinical thinking and problem analysis ability.
文摘Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with hydrogen(H2) breath tests and correlated to carbohydrate malabsorption. During performing these H2-breath tests the patient presented with an acute, localized, non-migratory pain in the left lower abdominal quadrant. Primary epiploic appendagitis is a rare cause of abdominal acute or subacute complaints and diagnosis of primary epiploic appendagitis(PEA) is made when computed tomography reveals a characteristic lesion. We report on a patient with cooccurrence of lactose and fructose malabsorption, which was treated successfully with a diet free of culprit carbohydrates, with PEA recovering without medication or surgical treatment within few days. Since the abdominal unspecific symptoms had been present for months, they appeared not to be correlated to the acute localized abdominal pain, therefore we speculate on a random co-occurrence of combined carbohydrate malabsorption and PEA.
文摘Background: Intravenous application of iron preparations which is a routine treatment of anemia in hemodialysis patients with end-stage renal disease can lead to iron overload in the body. Redox-active iron can catalyze the formation of hydroxyl radicals and initiation of lipid peroxidation, increase oxidative stress and speed up the development of complications in these patients. Objective: In this study, we determined the markers of lipid peroxidation, protein oxidation and antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, glutathione S-transferase) in serum of patients with end-stage renal disease on hemodialysis, who had received repeated treatment of iron supplementation. Patients and Methods: The study included 29 patients undergoing regular hemodialysis treatment. These patients were divided into three groups according to the serum ferritin levels: group I (serum ferritin between 100 and 300 mg/L);group II (serum ferritin between 301 and 600 mg/L), and group III (serum ferritin above 601 mg/L). Results: The serum of patients with the highest concentration of serum ferritin and iron contained significantly higher level of lipid peroxidation products, total hydroperoxides and malondialdehyde and advanced oxidation protein products and the lowest concentration of sulfhydryl groups, reduced glutathione and total antioxidant capacity. Conclusion: Based on the obtained results, it can be concluded that iron supplementation in hemodialysis patients and consequently body iron overload of exacerbated oxidative stress have already been present in these patients.
基金Supported by the European Union’s Horizon 2020 research and innovation programme,No.675228the Austrian Science Fund(FWF),No.P 29948-B28
文摘The extracellular calcium-sensing receptor(CaSR) is best known for its action in the parathyroid gland and kidneys where it controls body calcium homeostasis. However, the CaSR has different roles in the gastrointestinal tract, where it is ubiquitously expressed. In the colon, the CaSR is involved in controlling multiple mechanisms, including fluid transport, inflammation, cell proliferation and differentiation. Although the expression pattern and functions of the CaSR in the colonic microenvironment are far from being completely understood, evidence has been accumulating that the Ca SR might play a protective role against both colonic inflammation and colorectal cancer. For example, CaSR agonists such as dipeptides have been suggested to reduce colonic inflammation, while dietary calcium was shown to reduce the risk of colorectal cancer. CaSR expression is lost in colonic malignancies, indicating that the CaSR is a biomarker for colonic cancer progression. This dual anti-inflammatory and anti-tumourigenic role of the CaSR makes it especially interesting in colitisassociated colorectal cancer. In this review, we describe the clinical and experimental evidence for the role of the CaSR in colonic inflammation and colorectal cancer, the intracellular signalling pathways which are putatively involved in these actions, and the possibilities to exploit these actions of the CaSR for future therapies of colonic inflammation and cancer.
基金Supported by Lanzhou City Science and Technology Development Plan,No.2009-1-52
文摘AIM: To investigate the protective effects of remote ischemic postconditioning (RIP) against limb ischemia-reperfusion (IR)-induced gastric mucosal injury.
文摘Objective To investigate the role of oxidative stress, inflammation, hypercoagulability and neuroendocrine activation in the transition of hypertensive heart disease to heart failure with preserved ejection fraction （HFPEF）. Methods We performed echocardiography for 112 patients （≥ 60 years old） with normal EF （18 controls and 94 with hypertension）, and determined protein carbonylation （PC）, and tetrahydrobiopterin （BH4）, C-reactive protein （CRP）, interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α）, fibrinogen, plasminogen activator inhibitor type-I （PAI-I）, von Willebrand factor, chromogranin A （cGA） and B-type natriuretic peptide （BNP） levels from their blood samples. Results We found that 40% （38/94） of the patients with hypertension （HT） had no diastolic dysfunction （HTDD-）, and 60% （56/94） had diastolic dysfunction （HTDD＋）. Compared to the controls, both patient groups had increased PC and BH4, TNF-α, PAI-I and BNP levels, while the HTDD＋ group had elevated cGA and CRP levels. Decreased atrial and longitudinal left ventficular （LV） systolic and diastolic myocardial deformation （strain and strain rate） was demonstrated in both patient groups versus the control. Patients whose LV diastolic function deteriorated during the follow-up had elevated PC and IL-6 level compared to their own baseline values, and to the respective values of patients whose LV diastolic function remained unchanged. Oxidative stress, inflammation, BNP and PAI-I levels inversely correlated with LV systolic, diastolic and atrial function. Conclusions In patients with HT and normal EF, the most common HFPEF precursor condition, oxidative stress and inflammation may be responsible for LV systolic, diastolic and atrial dysfunction, which are important determinants of the transition of liT to HFPEF.
基金supported by the Slovenian Research Agency grants P3310,J3 3632,J3 4051,J3-4146,J3 6790,J3 7605
文摘Synthetic biology is the design and construction of new biological parts,devices,and systems,and the re-design of existing,natural biological systems for useful purposes.This new interdisciplinary effort has gained interest from the industry sector,and synthetic biology has been used to produce fragrances,such as vanillin in yeast,in cells that do not normally exist in nature.
基金supported by grants from The Fundamental ResearchFunds for the Central Universities(223000/862631)The National Natural Science Foundation of China(81773147)The Natural Science Foundation of Hunan Province,China(2015JJ2181)
文摘Despite progresses achieved in the therapy of tumors, the prognosis of patients is still limited by reccurence of residual tumor cells. Cancer cell dormancy plays a pivotal role in cancer relapse and drug resistance. In recent years, tumor cells undergoing EMT(epithelial-mesenchymal transition), CSCs(cancer stem cells) and CTCs(circulating tumor cells) are proved to share some common characteristics and show a cell cycle arrest phenotype. Thus, understanding the dormant stage of tumor cells could facilitate us in discovering ways to accelerate the development of tumor therapy and prevent its reccurence. In this review, we summarize the specific process of tumor cell dormancy induced by pharmacotherapy, and consider that dormancy is an initiative response rather than a passive defense to cytotoxicity. Besides, we probe into the mechanisms of tumor cell dormancy-mediated drug resistance, anticipating paving a way to target dormant tumor cells and result in better clinical outcomes.
文摘Complement activation-related pseudoallergy (CARPA) is a frequent side effect of intravenous therapies with nanoparticle-containing drugs and biologicals that are recognized by the immune system as foreign. It is an acute infusion reaction dominated by cutaneous and hemodynamic changes, most significantly a cardiopulmonary distress involving major pulmonary hypertension, systemic hypotension and arrhythmias. Because CARPA is unpredictable by conventional allergy tests and it may be life threatening, it can represent a major barrier to the safe therapeutic application of many modern medicines, including liposomal drugs and monoclonal antibodies. This review summarizes and updates the facts and opens questions regarding this phenomenon, with particular focus on its porcine model.
文摘Introduction: Pelvic floor muscle function of 30 overweight postmenopausal women prior to and after colporrhahpy was monitored in this study. Material and Methods: Patients diagnosed with cystokele or combined cystorectokele was involved. 1 mg oral estriol and local estriol cream were administered for 30 days preoperatively. Pelvic floor muscle function was monitored by surface electromyography 1 month before (1st) 1 day prior to surgery (2nd), and six weeks after the surgery (3rd measurement). Body composition parameters (intra- and extracellular water and body fat) were also measured. Results: The ability to relax significantly improved (p = 0.03) in the preoperative period (between 1st and 2nd occasions). Six weeks after surgery a non-significant (p = 0.054) decrease in average muscle activity was detected when compared with values obtained before the surgery. Muscle-activity declined significantly from the first to the last measurements (p = 0.005). Conclusion: Our results confirm that postmenopausal obese women who undergo anterior or posterior colporrhaphy need a follow-up concerning pelvic floor muscle function and suggest that physiotherapy started the earliest possible may aid in preserving postoperative functionality on the long run.
文摘The modulation of mechanically induced tracheobronchial cough was tested by applying various stimuli and the elicitation of other airway protective behaviors in pentobarbital anesthetized cats. Capsaicin and histamine were injected in the nose, and mechanical nylon fiber and/or air puff stimulation was applied to the nose and nasopharynx. Reflex responses of cough, sneeze, aspiration reflex and expiration reflex were induced mechanically. Swallow was initiated by the injection of water into oropharynx. Subthreshold mechanical stimulation of nasopharyngeal and nasal mucosa, as well as water stimulation in the oropharynx and larynx, with no motor response, had no effect on rhythmic coughing. Cough responsiveness and excitability increased with capsaicin and air puff stimuli delivered to the nose. Vice versa, the number of cough responses was reduced and cough latency increased when aspiration reflexes (>1) occurred before the cough stimulus or within inter-cough intervals (passive E2 cough phase). The occurrence of swallows increased the cough latency as well. Cough inspiratory and/or expiratory motor drive was enhanced by the occurrence of expiration reflexes, swallows, and sneezes and also by aspiration reflex within the inspiratory phase of cough and by nasal air puff stimuli. Complex central interactions, ordering and sequencing of motor acts from the airways may result in the disruption of cough rhythmic sequence but also in the enhancement of cough. Our data confirm that number of peripheral stimuli and respiratory motor responses significantly alters cough performance. We propose developing and testing stimulation paradigms that modify coughing and could be employed in correcting of inappropriate or excessive coughing.
文摘Background: Multiple organ dysfunction syndrome(MODS) is the sequential failure of several organ systems after a trigger event, like cardiogenic shock or decompensated heart failure. Mortality is high, up to 70% . Autonomic dysfunction(AD)may substantially contribute to the development of MODS. In cardiology, it has recently been shown that nonlinear parameters could predict mortality.Our study aimed at 1. characterising the complex characteristics of AD of critically ill MODS patients by the nonlinear parameters of autonomic information flow(AIF), 2. comparing AIF with autonomic function of healthy controls, and 3. characterising the accuracy of this parameter in predicting mortality in MODS. Methods: We enrolled 43 score-defined MODS patients who were consecutively admitted to a twelve-bed medical intensive care unit in a university centre into this prospective outcome study. Additionally, we assigned 50 healthy controls to the study. AIF was assessed as a complexity function of AD using 24-h ECG. Measures of AIF were introduced according to the standard HRV concept. The patients were followed up for 28-day mortality. Results: MODS causes a disorganisation of short term AIF in favour of an enhanced(rigid) long term AIF. Concerning prognosis increased short term AIF was associated with survival. Short term AIF discriminated between MODS survivors and nonsurvivors at the level of APACHE II score. Conclusions: This is the first study providing evidence that complex AD of MODS patients is specifically assessed by AIF time scales and that AIF has significant prognostic impact.
文摘Background：The main goals of flexor tendon surgery are to restore digital motion by providing tendon healing and to preserve tendon gliding.Our purpose was to investigate the effects of 5-fluorouracil （5-FU） on tendon adhesions in partially divided profundus flexor tendons （flexor digitorum profundus [FDPs]） following surgical repair and in partially divided FDPs without surgical repair,and to compare the results of the repair versus the nonrepair of zone two injuries via macroscopic and biomechanical evaluations of tendon adhesions.Methods：We used 32 adult male European rabbits （Oryctolagus cunniculus） weighing from 2.5 to 3.5 kg.The study was performed on the deep flexor tendons of the second and third digits of the right hind paws of the rabbits;thus,a total of 64 tendons were examined in this study.Results：Based on the results achieved in our experimental study,the load （N） significantly increased in subgroup 1a in which the tendons were surgically repaired and were not treated with 5-FU compared with subgroup 2a in which tendons were surgically repaired and treated with 5-FU.Conclusions：The load （N） significantly increased in subgroup 1 a in which the tendons were surgically repaired and were not treated with 5-FU compared to subgroup 2a in which the tendons were surgically repaired and treated with 5-FU.Therefore,these results revealed a decrease in adhesion formation in the subgroup that was treated with 5-FU due to increased resistance to tendon adhesions during their excursion through the tendon sheath,which in this case required greater traction force.
基金grants from NSFC-RSF(82261138557)the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202003)+3 种基金the Sichuan Science and Technology Program(2022YFH0006)Y.T.was supported by NSFC(82274668,82230127)Sichuan Provincial Administration of Traditional Chinese Medicine(2023zd024).Work in the M.V.S.laboratory is supported by National Institutes of Health(NS084030)by the Dr.Miriam and Sheldon G.Adelson Medical Foundation.
文摘Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder outcome.Pathophysiological changes in astroglia can be primary or secondary and can result in gain or loss of functions.Astroglia respond to external,non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure,molecular expression,and function.In addition,internally driven,cell autonomous changes of astroglial innate properties can lead to CNS pathologies.Astroglial pathophysiology is complex,with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder,disorder-stage,comorbidities,age,and sex.Here,we classify astroglial pathophysiology into(i)reactive astrogliosis,(ii)astroglial atrophy with loss of function,(iii)astroglial degeneration and death,and(iv)astrocytopathies characterised by aberrant forms that drive disease.We review astroglial pathophysiology across the spectrum of human CNS diseases and disorders,including neurotrauma,stroke,neuroinfection,autoimmune attack and epilepsy,as well as neurodevelopmental,neurodegenerative,metabolic and neuropsychiatric disorders.Characterising cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies.
